CORE--PATHOLOGY PROGRAM

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The Pathology Core plays a supportive role in the grant by providing anatomic and hematopathology data. The group has four research activities involving: 1) graft-versus-host disease (GVHD), 2) interstitial pneumonia, 3) veno-occlusive disease, and 4) viral diagnostic histology. These activities deal with important problems in the pathogenesis of, and methodology for improving the diagnosis and treatment of the diseases of bone marrow transplantation. Activity 1 tests the stem cell hypothesis of GVHD targeting as a way of gaining new insights into the pathogenesis of GVHD at the effector level. Its aims are to provide better predictive value specificity and sensitivity tests for GVHD and improve the distinction between pseudo-GVHD occurring in syngeneic and autologous patients and true GVHD. This includes a method of predicting early GVHD before day 21. Activity 2 addresses a new distinction within the noninfectious pneumonia group and deals with bronchoalveolar lavage detection methods for these conditions. It predicts different pathogenesis for diffuse alveolar damage and interstitial pneumonia and implies different therapies. Activity 3 proposes a new way to predict the risk of veno-occlusive disease of the liver based on immunohistological study of liver biopsies in transplant patients with and without prior liver inflammation. Activity 4 deals with improved viral diagnosis by 1) polymerase chain reaction detection of early cytomegalovirus pneumonia in bronchoalveolar lavage specimens, 2) the study of viral latency by detecting the genes for early antigens as signals for activation of latent disease, 3) the development of new single-stranded probes for improved viral diagnosis, 4) development of multiple in situ hybridization screening panel for four viruses (cytomegalovirus, HSV-1, HSV-2 and VZV) using pcr probes, and 5) improved Y chromosome in situ hybridization detection by the use of combined Y and X chromosome probes.